Prognostic factors of in-hospital complications after hip fracture surgery: a scoping review.

INTRODUCTION: To examine prognostic factors that influence complications after hip fracture surgery. To summarize proposed underlying mechanisms for their influence. METHODS: We reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Scoping Review extension. We searched MEDLINE, Embase, CINAHL, AgeLine, Cochrane Library, and reference lists of retrieved studies for studies of prognostic factor/s of postoperative in-hospital medical complication/s among patients 50 years and older treated surgically for non-pathological closed hip fracture, published in English on January 2008-January 2018. We excluded studies of surgery type or in-hospital medications. Screening was duplicated by two independent reviewers. One reviewer completed the extraction with accuracy checks by the second reviewer. We summarized the extent, nature, and proposed underlying mechanisms for the prognostic factors of complications narratively and in a dependency graph. RESULTS: We identified 44 prognostic factors of in-hospital complications after hip fracture surgery from 56 studies. Of these, we identified 7 patient factors-dehydration, anemia, hypotension, heart rate variability, pressure risk, nutrition, and indwelling catheter use; and 7 process factors-time to surgery, anesthetic type, transfusion strategy, orthopedic versus geriatric/co-managed care, multidisciplinary care pathway, and potentially modifiable during index hospitalization. We identified underlying mechanisms for 15 of 44 factors. The reported association between 12 prognostic factors and complications was inconsistent across studies. CONCLUSIONS: Most factors were reported by one study with no proposed underlying mechanism for their influence. Where reported by more than one study, there was inconsistency in reported associations and the conceptualization of complications differed, limiting comparison across studies. It is therefore not possible to be certain whether intervening on these factors would reduce the rate of complications after hip fracture surgery.

Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs.

Hyaluronic acid (HA) and recombinant human insulin were co-spray dried to form a dry powder suitable for inhalation (Mass Median Aerodynamic Diameter, MMAD=1 to 4 microm). Insulin systemic levels and corresponding glucose levels were monitored following administration of the microparticles to the lungs of male Beagle dogs. Release kinetics were modified by addition of excess zinc ions (Zn2+) or hydroxypropyl cellulose (HPC). HA formulations containing insulin (10%w/w) were found to extend the mean residence time (MRT) and terminal half-life (t(1/2)) when compared to spray dried pure insulin. Addition of Zn2+ also improved MRT (>9 fold), AUC/dose (2.5 fold) and Tmax (by a factor of 3) when compared to spray dried pure insulin. Addition of HPC improved MRT (>7 fold), AUC/dose (5 fold) and Tmax (by a factor of 3) when compared to spray dried pure insulin. Our results demonstrate the potential of HA-based dry powder drug delivery systems in the pulmonary controlled release of insulin.

Modifying the release of leuprolide from spray dried OED microparticles.

A range of oligosaccharide ester derivatives (OEDs) have been designed as drug delivery matrices for controlled release. The synthetic hormone analogue, leuprolide, was encapsulated within these matrices using hydrophobic ion pairing and solvent spray drying. The particles produced modified the release of leuprolide in vitro (dissolution in phosphate buffered saline) and in vivo (subcutaneous and pulmonary delivery in the rat). Release rate was dependent on drug loading and could be manipulated by choice of OED and by combining different OEDs in different ratios. Leuprolide encapsulated in the OEDs retained biological activity as evidenced by elevation in plasma luteinising hormone levels following subcutaneous injection of leuprolide recovered from OED particles in vitro prior to in vivo administration.

Early predictors of myoglobinuria and acute renal failure following electrical injury.

Myoglobinuria-induced acute renal failure (ARF) is a potentially lethal consequence of electrical injury. We describe clinical variables that can predict the risk of myoglobinuria and ARF following electrical injury. This was a retrospective multivariate analysis of risk factors among electrically injured patients over a 26-year period. Urine myoglobin status was documented in 162 patients; 14% had myoglobinuria. No patient developed ARF. Multivariate modeling revealed that high-voltage exposure, prehospital cardiac arrest, full-thickness burns, and compartment syndrome were associated with myoglobinuria. Using a prediction rule defined as positive when a patient had > or = 2 risk factors yielded a sensitivity of 96% and negative predictive value of 99%. Electrical injury patients with myoglobinuria have little risk of developing ARF. A prediction rule can be used to screen out patients at low risk for myoglobinuria and identify high-risk patients who warrant early aggressive treatment and a more definitive myoglobin test.

Mechanisms of pediatric electrical injury. New implications for product safety and injury prevention.

OBJECTIVES: To determine age-specific mechanisms of electrical injury in children, to examine product safety regulation of the major sources of electrical injury hazard, and to assess the adequacy of current prevention strategies. DESIGN: Case series of 144 pediatric and adolescent electrical injuries in patients seen in the specialized burn center and tertiary care hospital between 1970 and 1995, examination of Consumer Product Safety Commission product recall reports for electrical injury hazards between 1973 and 1995, and review of the National Electric Code. RESULTS: Eighty-six cases of electrical injuries resulted from low-voltage (< 1000-V) exposures, all occurring within the home. In children aged 12 years and younger, household appliance electrical cords and extension cords caused more than 64 (63%) of 102 injuries, whereas wall outlets were responsible for only 14 (15%) of injuries. Fifty-eight cases resulted from high-voltage exposures, accounting for 38 (90%) of 42 injuries in children older than 12 years. No federal safety regulations for electrical cords exist, although voluntary standards have been adopted by many manufacturers. Among 383 consumer products identified by the Consumer Product Safety Commission to be electrical injury hazards, 119 were appliance cords, extension cords, or holiday stringed light sets. Several products numbered more than 1.5 million units in US household distribution prior to the investigation by the Consumer Product Safety Commission. CONCLUSIONS: Household electrical cords are the major electrocution hazard for children younger than 12 years, yet no federal safety mandates exist. Despite voluntary standards, noncompliant manufacturers can introduce vast numbers of unsafe cords onto the US household market every year. Conversion of existing voluntary safety guidelines into federally legislated standards may be the most effective intervention against pediatric electrocutions.

Mechanisms of aluminum absorption in rats.

Aluminum has become a dietary toxin in modern times but its mechanism of absorption is poorly understood. After ingestion, the systemic transfer of aluminum is small but it is greatly affected by the coingestion of certain dietary agents, such as citrate, that complex with the metal in the intestinal lumen or transiently alter the permeability of the mucosa. Here, mechanisms of aluminum absorption were studied by using freshly prepared aluminum hydroxide and aluminum citrate. Everted sacs of rat gut were used to investigate the site of absorption, effect of chemical charge on absorption of aluminum citrate, and presence of active or passive absorption with use of the metabolic inhibitor ouabain. Absorption was biphasic with a large tissue uptake that was consistent with adhesion to mucus-mucosal surface but little tissue transport, which was consistent with passive paracellular permeation. Citrate reduced the uptake-transport ratio both by competing with the mucosal uptake and by increasing mucus-mucosal permeation but not by affecting the charge of the luminal aluminum species. Despite the potential for hydroxypolymerization of aluminum at intestinal pH, the small bowel and colon absorbed aluminum passively and paracellularly but the stomach did not. The predominantly proximal absorption of aluminum observed in vivo is a reflection of the proximal absorption, and therefore removal, of dietary constituents (eg, citrate) that enhance mucosal permeation of aluminum. The colon should be investigated further as a site of significant paracellular permeability.

Gallium-transferrin binding in treated and untreated Parkinson's disease.

The binding of gallium (Ga) to transferrin (Tf) was studied in plasma from control patients, in patients with untreated Parkinson's disease (PD) and in patients with PD treated either with levodopa (L-dopa) alone or in combination with selegiline. Mean percentage Ga-Tf binding was significantly reduced in untreated and treated PD compared with controls. Binding, however, was significantly greater in treated than in untreated patients. There was no difference in binding between patients treated with L-dopa alone and those treated with L-dopa and selegiline. The data support the hypothesis that oxidation reactions may be of pathogenic significance in PD.

Aluminium and Alzheimer's disease: review of possible pathogenic mechanisms.

Chronic exposure to aluminium (Al) remains a controversial possible cause of sporadic forms of Alzheimer's disease (AD). This article reviews the evidence that once Al enters the brain and individual brain cells, it may be involved in three pathological processes: (1) the production of abnormal forms of tau leading to the formation of cellular neurofibrillary tangles and neuropil threads; (2) the processing of the amyloid precursor protein, resulting in the formation of beta-amyloid deposits and senile plaques, and (3) that via the mutual histocompatibility system, Al could be involved in the initiation of the immune response observed in AD patients. Despite recent evidence that Al could be involved in these processes, a conclusive case that exposure to Al initiates the primary pathological process in sporadic AD remains to be established.

Strain difference in growth of AHA and Han Wistar rat embryos in vivo and after extended culture in vitro.

Recently, a rationalization of strains used in our laboratories has led to the adoption of the Han Wistar rat as the standard strain for repeat dose and reproductive toxicity studies. Earlier work on developing an extended whole embryo culture model in which AHA (Allen and Hanbury Albino) rats were grown from day 10 to day 14 of pregnancy was therefore repeated in the Han Wistar strain. Differences were seen in rate of embryonic growth in vivo for the two strains of rat, particularly in terms of crown-rump length and protein content. No such differences were seen in rate of morphological development. Extending the period of whole embryo culture up to day 14 of pregnancy using a novel protocol further illustrated these differences in growth characteristics. Results showed marked differences in growth, but not in general morphological development, when a standard culture technique was used. These findings indicate that accepted standard culture regimens are unsuitable for some strains of rat, and that the development of strain-specific methodology must be considered when such models are to be used for mechanistic studies.

The role of pterins in depression and the effects of antidepressive therapy.

Urinary excretion of neopterins (N) and biopterins (B) was measured in 48 patients with depression before and after treatment with placebo, antidepressants, or electroconvulsive therapy (ECT), and in 26 healthy control subjects. Patients prior to and after treatment had a significantly greater neopterin/biopterin (N:B) ratio than control subjects. There was a significant correlation between N:B ratios and the severity of depression and plasma cortisol. As a raised N:B ratio implies failure to convert neopterin to biopterin, it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate-limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive illness.

Hypothesis: is Alzheimer's disease a metal-induced immune disorder?

A hypothesis that a metal-induced immune disorder may be involved in the pathogenesis of some forms of Alzheimer's disease (AD) is presented. The classical complement pathway is activated in AD and T cells and reactive microglia appear in the brain. Studies of metal induced autoimmunity and the use of compounds containing aluminium as vaccine adjuvants suggest that metals can activate complement and can be taken up by antigen presenting cells. The consequent immune response could contribute to neuronal damage, beta-amyloid deposition and cell death. The strengths and weaknesses of this hypothesis are discussed and tests of some aspects are proposed.

5-Methyltetrahydrofolate level in the serum of depressed subjects and its relationship to the outcome of ECT.

Serum 5-MeTHF levels are reported in 26 subjects, before and after completing a course of ECT, and compared to 21 healthy volunteers. 5-MeTHF levels of depressed subjects were significantly lower than controls before and after ECT. There was no difference in 5-MeTHF levels between ECT responders and non-responders but folate deficiency was related to severity of depression before ECT. Serum 5-MeTHF was not related to treatment response and values remained markedly low even after a good response to treatment.

Recovery from depression after electroconvulsive therapy is accompanied by evidence of increased tetrahydrobiopterin-dependent hydroxylation.

Serum phenylalanine and tyrosine levels were measured in 26 patients with severe depression before and after receiving electroconvulsive therapy. The phenylalanine:tyrosine [P:T] ratio declined significantly for those responding to treatment but not for nonresponders. These findings are discussed in relation to tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, dopamine and serotonin and the hydroxylation of phenylalanine to tyrosine.

Pre-injury emotional trauma and chronic back pain. An unexpected finding.

STUDY DESIGN: A retrospective study investigated pre-injury emotional trauma in out-of-work, blue collar patients with chronic back pain (N = 27) who participated in a 30-hour workshop in which a wide range of cognitive skills was taught to help patients with rehabilitation and return them to work. OBJECTIVES: This study identified categories of pre-injury emotional trauma, calculated summary statistics, and performed category comparisons. METHODS: The categories of abandonment, emotional abuse, physical abuse, and sexual abuse emerged from the data. Frequencies and percentages in each category were calculated. Chi-square tests compared the differences in emotional trauma and gender. RESULTS: Statistically more patients reported abandonment and emotional abuse than physical and sexual abuse. There were no differences in trauma rates by gender. The results of the study revealed a high rate of pre-injury emotional trauma in patients with chronic back pain. CONCLUSION: Including pre-injury emotional trauma in psychologic evaluations of patients with chronic back pain and high psychologic test scores is recommended.

Reduced transferrin binding in Down syndrome: a route to senile plaque formation and dementia.

Plasma transferrin binding in Down syndrome and Alzheimer's disease is significantly reduced compared with age matched controls and it was thought this may help elucidate a pathological time sequence for the onset of dementia in Down syndrome. In Down syndrome, there was a reduction in gallium and aluminium transferrin binding both with age and the onset of dementia. Non-transferrin bound gallium species were identified as non-transportable phosphate or silicate. Thus, the route of entry of metals into the brain must be via a transferrin mediated complex only. A clear sequence of pathological events has been demonstrated in Down syndrome which shows the pathway to development of plaques and dementia and this is believed to have an immunological origin.

Pterin metabolism in depression: an extension of the amine hypothesis and possible marker of response to ECT.

Urinary excretion of neopterins and biopterins was measured in 23 patients with severe depression before and after receiving electroconvulsive therapy (ECT) and 26 healthy control subjects. Patients with psychotic depression and those responding to ECT had neopterin:biopterin (N:B) ratio significantly higher than controls before commencing ECT and positive therapeutic response was associated with reduction of N:B ratio towards control values. As a raised N:B ratio implies failure to convert neopterin to biopterin it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive disorders. The N:B ratio may be a marker for certain depressive subtypes and response to ECT.

Aluminium administered in drinking water but not in the diet influences biopterin metabolism in the rodent.

To investigate the neurotoxic effects of aluminium (Al) Al was administered: 1) in the diet of the rat (30 mg Al/kg body weight for 6 weeks); 2) as a suspension of aluminium acetate in drinking water of the rat for 3 months and 3) in a long-term study in the mouse in which aluminosilicates were incorporated into a pelleted diet (1035 mg/kg of food over 23 months). In the latter treatment, increased Al was combined with a reduction in calcium and magnesium; a treatment designed to increase absorption of Al into the body. Administration of Al in the drinking water significantly reduced total brain biopterins and BH4 synthesis. However, no significant affect of Al in the diet on total biopterins or BH4 synthesis was found either in the rat or in the long-term study in the mouse. In addition, in the mouse no significant effects of the Al diet on levels of noradrenaline, serotonin, dopamine, 5-HIAA or CAT could be demonstrated. Hence, the occurrence of brain alterations may depend on the Al species present and the method of administration. Al salts in drinking water may increase brain tissue levels compared with the administration of a more insoluble species. Since alterations in biopterin metabolism are also a feature of Alzheimer's disease (AD) these results support the hypothesis that Al in the water supply may be a factor in AD.